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(PSYCHIATRIC TIMES) - Phobias, obsessions and compulsions, and symptoms of posttraumatic stress are often poorly responsive to conventional drugs.2 In the context of efficacy and safety issues associated with conventional treatments for anxiety, psychiatrists should know about the evidence for nonconventional therapy. In Part 1 of this article, I review research findings on the most substantiated nonpharmacological and integrative treatments for anxiety. In Part 2, I will discuss less substantiated but promising nonconventional approaches.

Positive research findings consistently support the use of kava and L-theanine in the treatment of persons with generalized anxiety. Regular relaxation, meditation, and mindfulness practices improve symptoms of generalized anxiety, and these nonpharmacological therapies may be safely combined with conventional drugs. Virtual reality graded exposure therapy (VRGET) will play a significant role in the treatment of many anxiety disorders that respond poorly to currently available treatments, such as drugs and cognitive-behavioral therapy (CBT). Numerous studies show that electroencephalographic (EEG) and electromyographic (EMG) biofeedback are as effective as regular relaxation training or mind-body practices for the treatment of moderately severe symptoms of generalized anxiety. A growing body of evidence supports the use of microcurrent stimulation of the CNS for the management of generalized anxiety.

Less-substantiated treatments for anxiety will be reviewed in Part 2 of this column and include dietary changes, supplementation with l-tryptophan or 5-hydroxytryptophan, regular exercise, massage, acupuncture (including electro-acupuncture), healing touch, and Reiki.
Kava (Piper methysticum)

When kava is used at recommended dosages (typically 60 to 300 mg/d), patients do not experience the mental slowing or impaired cognitive functioning that is typical of many conventional anti-anxiety medications.3 Animal studies suggest that the mechanism of action involves serotonin blockade in the amygdala by alpha-pyrones, a principal bioactive constituent of kava.

Kava also interferes with norepinephrine reuptake and has a high binding affinity with g-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) receptors. Kava may also modulate vagal heart tone in patients with generalized anxiety.4

A systematic review of 11 controlled, double-blind studies that included more than 600 patients concluded that kava was superior to placebo for the short-term management of generalized anxiety.5 Randomized, controlled, double-blind studies support the use of kava preparations that are standardized to 70% kava lactones in divided doses of 70 to 240 mg/d for the treatment of "stress" and moderate anxiety but not for severe anxiety or agitation.6,7 Daily use of standardized kava preparations of 100 to 200 mg was found to effectively reduce anxiety symptoms associated with menopause.8

Kava compares favorably with benzodiazepines and other conventional anti-anxiety drugs. The findings of a small, double-blind, controlled trial suggest that patients who have generalized anxiety who gradually increased their daily dose of kava (up to 300 mg) while tapering off a benzodiazepine did not experience worsening anxiety or benzodiazepine withdrawal.9

A randomized, placebo-controlled, multicenter study of 129 outpatients concluded that a standardized kava preparation (LI 150) was as effective as 2 commonly prescribed anti-anxiety agents (buspirone [BuSpar] and opipramol [Insidon], which is commonly prescribed in Germany) for the treatment of generalized anxiety.10 Three fourths of patients in both the kava group and the conventional drug group experienced 50% or greater reductions in Hamilton Anxiety Scale scores and were classified as "treatment responders."

Kava is generally well tolerated, even at doses significantly above typical therapeutic doses.Uncommon adverse effects include GI upset, rash, headache, and dizziness.11 In recent decades, there have been reports of kava inebriation,12 although this social phenomenon has not been observed in Europe, where kava preparations are used medicinally to treat anxiety. Kava does not potentiate the effects of alcohol consumption in humans. Rare case reports suggest that kava may cross-react with benzodiazepines, increasing their sedating effects.13 Reports of hepatitis14 and fulminant liver failure have led to restrictions in the sale of kava products in many European countries and to a warning issued by the FDA.15 These cases were rare, however, and independent experts have concluded that most reported cases of liver failure were associated with a processing error that resulted in toxic levels of alkaloids in a single batch of kava.16,17

In view of these safety issues, patients should be advised against taking kava18 when there is a question of alcohol abuse or concurrent use of conventional sedative-hypnotics. One case report suggests that kava may interfere with anti-parkinsonian drugs.19
L-Theanine (gamma-ethylamino-L-glutamic acid)

Green tea is used as a restorative in traditional Chinese medicine and contains many bioactive constituents, including the amino acid L-theanine. The anti-anxiety effect of L-theanine is achieved through enhanced alpha brain wave activity and increased synthesis of GABA.20,21 Greater GABA levels, in turn, increase the brain's levels of dopamine and reduce serotonin levels, resulting in general feelings of calm and well-being.22 Changes in brain electrical activity, as measured with EEG, are dose-dependent and are similar to the beneficial EEG changes observed in meditation, including increased alpha waves in the occipital and parietal regions.23 A calming effect is usually noted within 30 to 40 minutes after L-theanine is taken at doses of 50 to 200 mg, and typically lasts 8 to 10 hours. Moderate anxiety symptoms often improve in patients taking 200 mg once or twice daily. More severe anxiety symptoms may require dosages of 600 to 800 mg/d, taken in divided doses of 100 to 200 mg.

Unlike benzodiazepines and other conventional anti-anxiety treatments, L-theanine does not result in increased drowsiness, slowed reflexes, or impaired concentration. There is no risk of tolerance or dependence developing, and there have been no reports of serious adverse effects or interactions with other natural products or conventional drugs.
Applied relaxation comparable to cognitive therapy

Applied relaxation is a generic term for somatic or mind-body exercises used to diminish generalized anxiety. Relaxation techniques include sustained deep breathing,24 progressive muscle relaxation, guided imagery, and systematic desensitization. Several models have been proposed to explain the anxiety-reducing effects of mind-body practices, including Benson's relaxation response and Selye's general adaptation syndrome. One model posits that anxiety is associated with muscle tension and is reduced by behaviors or cognitions that diminish tension and autonomic arousal. The effectiveness of relaxation as a treatment of various anxiety symptoms has been extensively reviewed.25

Guided imagery is widely used as a self-directed treatment of generalized anxiety. Applied relaxation techniques are often practiced together with mental imagery, meditation, or mindfulness training. Imagery can be individualized to the specific anxiety symptoms of each patient and is known to have beneficial effects on the immune system, physiological stress responses, and cognitive-emotional functioning in general.26 The consistent practice of mental imagery effectively reduces many kinds of anxiety symptoms, including generalized anxiety, feelings of panic, and traumatic memories.27,28 Imagery and relaxation techniques are often used together to induce hypnotic trance states, resulting in a dramatic reduction in symptoms of generalized anxiety.29

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